This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The lesion-bypass polymerases can synthesize DNA opposite damaged template bases and are hypothesized to replace replicative DNA polymerases that stall at lesion sites, allowing DNA replication to continue. Several subfamilies of these polymerases exist, with each displaying specificity for a unique set of lesions. When replicating undamaged DNA, the lesion-bypass polymerases have a very high error rate. We want to understand, at the molecular level, the lesion specificity of these polymerases, the types of errors made during replication, and how the different DNA polymerases in a cell are all coordinated so that replication is accurate and complete.